title: Immunotherapy of cerebrovascular amyloidosis in a transgenic mouse model.
abstract: Cerebrovascular amyloidosis is caused by amyloid accumulation in walls of blood vessel walls leading to hemorrhagic stroke and cognitive impairment. Transforming growth factor-β1 (TGF-β1) expression levels correlate with the degree of cerebrovascular amyloid deposition in Alzheimer's disease (AD) and TGF-β1 immunoreactivity in such cases is increased along the cerebral blood vessels. Here we show that a nasally administered proteosome-based adjuvant activates macrophages and decreases vascular amyloid in TGF-β1 mice. Animals were nasally treated with a proteosome-based adjuvant on a weekly basis for 3 months beginning at age 13 months. Using magnetic resonance imaging (MRI) we found that while control animals showed a significant cerebrovascular pathology, proteosome-based adjuvant prevents further brain damage and prevents pathological changes in the blood-brain barrier. Using an object recognition test and Y-maze, we found significant improvement in cognition in the treated group. Our findings support the potential use of a macrophage immunomodulator as a novel approach to reduce cerebrovascular amyloid, prevent microhemorrhage, and improve cognition.
authors.affiliation: Department of Neurobiology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Veronica
authors.initials: V
authors.lastname: Lifshitz
authors.forename: Ronen
authors.initials: R
authors.lastname: Weiss
authors.forename: Tali
authors.initials: T
authors.lastname: Benromano
authors.forename: Einat
authors.initials: E
authors.lastname: Kfir
authors.forename: Tamar
authors.initials: T
authors.lastname: Blumenfeld-Katzir
authors.forename: Catherine
authors.initials: C
authors.lastname: Tempel-Brami
authors.forename: Yaniv
authors.initials: Y
authors.lastname: Assaf
authors.forename: Weiming
authors.initials: W
authors.lastname: Xia
authors.forename: Tony
authors.initials: T
authors.lastname: Wyss-Coray
authors.forename: Howard L
authors.initials: HL
authors.lastname: Weiner
authors.forename: Dan
authors.initials: D
authors.lastname: Frenkel
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D016657:Cerebral Amyloid Angiopathy / Q000276:immunology* / Q000628:therapy*; D003546:Cysteine Endopeptidases / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004338:Drug Combinations; D007167:Immunotherapy / Q000379:methods; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D008262:Macrophage Activation / Q000187:drug effects*; D051379:Mice; D008822:Mice, Transgenic; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000276:immunology*; D016896:Treatment Outcome
chemical_list: D004338:Drug Combinations; D008070:Lipopolysaccharides; C493785:Protollin; D053773:Transforming Growth Factor beta1; D003546:Cysteine Endopeptidases